Abstract: This is a study employing functional magnetic resonance imaging (fMRI) and measures of appetiterelated hormone concentrations pre and post bariatric surgery. The mechanisms of reduced food intake and weight loss after obesity surgery are not well understood. Participants will be studied prior to surgery as well as 3 mo and 18 mo following the two most common operations world wide: laparoscopic gastric bypass (RYGB) and laparoscopic adjustable gastric banding (GB). These two operative groups will be compared to two control groups: 1) active weight loss on a formula diet (WL) for 3 mo; and 2) candidates for surgery who do not have an operation, or no treatment (NT). fMRI will be used to examine areas of brain activation in response to visual and auditory stimuli of palatable high energy foods, less palatable low energy foods, and non foods. At 3 mo, relative to study baseline, it is expected that there will be reduced activation in key brain areas, such as the prefrontal cortex, in response to the high-energy food stimuli after RYGB. In contrast, there should be an increase in activation in these areas after GB and to an even greater extent in WL and no change in NT. There will be some return in brain activation to baseline by 18 mo, especially for WL with expected weight regain, and no changes in NT. Both surgical operations restrict the size of the stomach, but RYGB is much more invasive than GB and involves sectioning the stomach and bypassing a segment of the intestine. The sectioning of the stomach may lead to lower levels of the orexigenic hormone, ghrelin, produced mainly by the stomach, and combined with the intestinal bypass, to higher post meal levels of the anorexigenic hormones, PYY and GLP-1. Hormones will be measured prior to and after a fixed liquid meal at each of the three time points. It is expected that GB, and to a greater extent WL, will experience changes in these hormones in the opposite direction from RYGB at 3 mo relative to study baseline, with some return to this baseline at 18 mo. As a secondary aim, we will assess eating disorders, focusing on binge eating disorder (BED), which are expected to decline the most after RYGB but to start to return at 18 mo. Presurgery eating disorders, particularly BED, and their changes post surgery will be examined and related to changes in brain activation, gut hormones, and weight loss. We will enroll 128 relatively healthy (nondiabetic) clinically severe obese men and women with a BMI of 40-50, with 32 RYGB, 32 GB, 32 WL, and 32 NT. The BMI range will ensure that virtually all S[unreadable]s will fit into the scanner. All four groups will be matched for BMI and for female to male ratio of about 3 to1, as well as for race. The findings should improve our knowledge of the biological mechanisms that contribute to appetite and weight reduction after bariatric surgery. This may lead to improvements in the surgical procedures and to new insights into basic mechanisms that lead to obesity, which could provide the basis for new less invasive treatments.